Retinoids, particularly retinoic acid, are able to suppress, prevent, and reverse the transformation of premalignant cells to the malignant state. Consequently, they have potential value as drugs for the chemoprevention and treatment of cancer. However, those retinoids tested to date have substantial toxic side effects. Therefore, new retinoids are required. The synthesis of a series of novel and potentially more effective retinoids is proposed. These compounds have conformational restrictions and electronic variations in the tetraene chain region of the retinoid skeleton. Compounds will be screened for chemopreventive efficacy with the ornithine decarboxylase and antipapilloma tumor assays. Their binding affinity to cellular retinoic acid-binding protein will be determined. Active compounds will be submitted to NCI for additional testing.